Noninvasive system for evaluating the allergen-specific airway response in a murine model of asthma

In the present report, we show that the enhanced pause (Penh), a novel indicator of airway responsiveness to bronchoconstrictors, can also be a good marker of airway response to an allergen challenge in a murine model of asthma. Male BALB/c mice were sensitized with ovalbumin (OVA) through a combination of intraperitoneal injection and aerosol inhalation. After this immunization, the OVA-specific IgE titer in serum increased to a significantly higher level than in a saline/PBS-treated control group. After the final OVA aerosol challenge, Penh was repeatedly measured in conscious, unrestrained mice, according to the time schedule. Penh increased gradually after the challenge and reached a maximal value at 24 hours that was significantly higher than the control value (p < 0.01). Histologic examination of the lung revealed airway inflammation with an invasion by eosinophils and lymphocytes from vessels into the peribronchial interstitium and the mucosal and submucosal areas of the bronchus. There was a strong correlation between the Penh value and eosinophil number in bronchoalveolar lavage fluid (r = 0.699, p < 0.0001). Moreover, Penh also correlated strongly with the intensity score of histologic findings. These results suggest that the bronchial response to a specific allergen could be followed in a particular individual through the noninvasive Penh method, and that Penh accurately reflects the intensity of eosinophilic bronchial inflammation. This system would be applicable to a noninvasive, chronological evaluation of various experimental interventions in a murine model of asthma.